Summary of Study ST001329

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000908. The data can be accessed directly via it's Project DOI: 10.21228/M8B11Q This work is supported by NIH grant, U2C- DK119886.

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Study IDST001329
Study TitleSS-31 and NMN: Two Paths to Improve Metabolism and Function in Aged Hearts
Study SummaryThe effects of two different mitochondrial-targeted drugs, SS-31 and NMN, were tested on Old mouse hearts. After treatment with the drugs, individually or Combined, heart function was examined by echocardiography. SS-31 partially reversed an age-related decline in diastolic function while NMN fully reversed an age-related deficiency in systolic function at a higher workload. Metabolomic analysis revealed that both NMN and the Combined treatment increased nicotinamide and 1-methylnicotinamide levels, indicating greater NAD+ turnover, but only the Combined treatment resulted in significantly greater steady state NAD(H) levels. A novel magnetic resonance approach was used to assess how metabolite levels responded to changing workload. PCr/ATP decreased in response to increased workload in Old Control, but not Young, hearts, indicating an age-related decline in energetic capacity. Both drugs were able to normalize the PCr/ATP dynamics. SS-31 and NMN treatment also increased mitochondrial NAD(P)H production under the higher workload while only NMN increased NAD+ in response to the work jump. These measures did not shift in hearts given the Combined treatment, which may be owed to the enhanced NAD(H) levels in the resting state after this treatment. Overall, these results indicate that both drugs are effective at restoring different aspects of mitochondrial and heart health and that combining them results in a synergistic effect that rejuvenates Old hearts and best recapitulates the Young state.
Institute
University of Washington
Last NameWhitson
First NameJeremy
Address1959 NE Pacific St, Seattle, WA, 98195, USA
Emailwhitsonj@uw.edu
Phone3307605189
Submit Date2020-03-18
Num Groups5
Total Subjects53
Num Males53
Raw Data AvailableYes
Raw Data File Type(s)wiff
Analysis Type DetailLC-MS
Release Date2020-04-03
Release Version1
Jeremy Whitson Jeremy Whitson
https://dx.doi.org/10.21228/M8B11Q
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN002215
Analysis type MS
Chromatography type HILIC
Chromatography system Shimadzu Nexera XR LC-20AD
Column Waters Acquity BEH Amide (150 x 2.1mm,1.7um)
MS Type ESI
MS instrument type Triple quadrupole
MS instrument name ABI Sciex 6500 QTrap
Ion Mode UNSPECIFIED
Units Peak Area

Chromatography:

Chromatography ID:CH001625
Chromatography Summary:Samples were injected into a chromatography system consisting of a dual injection valve setup allowing injections onto two different LC columns with each column dedicated to an ESI polarity. 5 µL were injected on the positive mode column and 10 µL on the negative side column. The columns were a matched pair from the same production lot number and were both a Waters XBridge BEH amide column (2.1 x 150 mm). Autosampler was maintained at 4 °C and column oven was set to 40 °C. 0.3 mL/min gradient was 0-3 min 95% B, 3-8 min 95 -> 50% B, 8-12 min 50% B, 12-13 min 50 – 95% B, 13-18 min 95% B. After completion of the 18 minute gradient, injection on the opposite column was initiated and the inactive column was allowed to equilibrate at starting gradient conditions. A set of QC injections for both instrument and sample QC were run at the beginning and end of the sample run.
Instrument Name:Shimadzu Nexera XR LC-20AD
Column Name:Waters Acquity BEH Amide (150 x 2.1mm,1.7um)
Column Temperature:40
Solvent A:95% water/3% acetonitrile/2% methanol; 0.2% acetic acid; 10 mM ammonium acetate
Solvent B:93% acetonitrile/5% water/2% methanol; 0.2% acetic acid; 10 mM ammonium acetate
Chromatography Type:HILIC
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